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Engineering death receptor ligands for cancer therapy.

Abstract：

:CD95, TNFR1, TRAILR1 and TRAILR2 belong to a subgroup of TNF receptors which is characterized by a conserved cell death-inducing protein domain that connects these receptors to the apoptotic machinery of the cell. Activation of death receptors in malignant cells attracts increasing attention as a principle to fight cancer. Besides agonistic antibodies the major way to stimulate death receptors is the use of their naturally occurring "death ligands" CD95L, TNF and TRAIL. However, dependent from the concept followed to develop a death ligand-based therapy various limiting aspects have to be taken into consideration on the way to a "bedside" usable drug. Problems arise in particular from the cell associated transmembrane nature of the death ligands, the poor serum half life of the soluble fragments derived from the transmembrane ligands, the ubiquitous expression of the death receptors and the existence of additional non-death receptors of the death ligands. Here, we summarize strategies how these limitations can be overcome by genetic engineering.

journal_name

Cancer Lett

journal_title

Cancer letters

authors

Wajant H,Gerspach J,Pfizenmaier K

doi

10.1016/j.canlet.2010.12.019

subject

Has Abstract

pub_date

2013-05-28 00:00:00

pages

163-74

issue

2

eissn

0304-3835

issn

1872-7980

pii

S0304-3835(10)00582-3

journal_volume

332

pub_type

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